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J Affect Disord. 2017 Nov;222:79-87. doi: 10.1016/j.jad.2017.06.055. Epub 2017 Jun 27.

Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

Author information

1
University Hospital Münster, Department of Clinical Radiology, Münster, Germany; University Hospital Heidelberg, Department of General Internal Medicine and Psychosomatics, Heidelberg, Germany.
2
University Hospital Münster, Department of Clinical Radiology, Münster, Germany. Electronic address: benedikt.sundermann@uni-muenster.de.
3
University of Münster, Institute of Epidemiology and Social Medicine, Münster, Germany.
4
University Hospital Münster, Department of Clinical Radiology, Münster, Germany.
5
University Hospital Münster, Department of Clinical Radiology, Münster, Germany; University of Münster, Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, Münster, Germany.

Abstract

OBJECTIVES:

Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification.

MATERIALS AND METHODS:

We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained.

RESULTS:

Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level.

LIMITATIONS:

It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data.

CONCLUSIONS:

Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity.

KEYWORDS:

Cluster-analysis; Depression; Diagnostic classification; Functional connectivity; Heterogeneity; Subtypes

PMID:
28679115
DOI:
10.1016/j.jad.2017.06.055
[Indexed for MEDLINE]

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